tbuckley/cabot-search huggingface dataset:
An HGF‐dependent positive feedback loop between bladder cancer cells and fibroblasts mediates lymphangiogenesis and lymphatic metastasis
Authors: Yuting Li, Hanhao Zheng, Yuming Luo, Yan Lin, Mingjie An, Yao Kong, Yue Zhao, Yina Yin, Le Ai, Jian Huang, Changhao Chen
Journal: Cancer Communications (2023)

Abstract Background Cancer‐associated fibroblasts (CAFs) play a vital role in facilitating tumor progression through extensive reciprocal interplay with cancer cells. Tumor‐derived extracellular vesicles (EVs) are the critical mediators involved in the crosstalk between cancer cells and stromal cells, contributing to the metastasis of cancers. Yet, the biological mechanisms of tumor‐derived EVs in triggering CAFs phenotype to stimulate the lymph node (LN) metastasis of bladder cancer (BCa) are largely unknown. Here, we aimed to explore the effects and molecular mechanisms of tumor‐derived EV‐mediated CAFs phenotype in regulating BCa LN metastasis. Methods The high‐throughput sequencing was utilized to identify the crucial long non‐coding RNA (lncRNA) associated with CAF enrichment in BCa. The functional role of the transition of fibroblasts to CAFs induced by LINC00665‐mediated EVs was investigated through the in vitro and in vivo assays. Chromatin isolation by RNA purification assays, fluorescence resonance energy transfer assays, cytokine profiling and patient‐derived xenograft (PDX) model were performed to explore the underlying mechanism of LINC00665 in the LN metastasis of BCa. Results We found that CAFs are widely enriched in the tumor microenvironment of BCa, which correlated with BCa lymphangiogenesis and LN metastasis. We then identified a CAF‐associated long non‐coding RNA, LINC00665, which acted as a crucial mediator of CAF infiltration in BCa. Clinically, LINC00665 was associated with LN metastasis and poor prognosis in patients with BCa. Mechanistically, LINC00665 transcriptionally upregulated RAB27B expression and induced H3K4me3 modification on the promoter of RAB27B through the recruitment of hnRNPL. Moreover, RAB27B‐induced EVs secretion endowed fibroblasts with the CAF phenotype, which reciprocally induced LINC00665 overexpression to form a RAB27B‐HGF‐c‐Myc positive feedback loop, enhancing the lymphangiogenesis and LN metastasis of BCa. Importantly, we demonstrated that blocking EV‐transmitted LINC00665 or HGF broke this loop and impaired BCa lymphangiogenesis in a PDX model. Conclusion Our study uncovers a precise mechanism that LINC00665 sustains BCa LN metastasis by inducing a RAB27B‐HGF‐c‐Myc positive feedback loop between BCa cells and fibroblasts, suggesting that LINC00665 could be a promising therapeutic target for patients with LN metastatic BCa.
PARP1 modulates METTL3 promoter chromatin accessibility and associated LPAR5 RNA m6A methylation to control cancer cell radiosensitivity
Authors: Xiaoya Sun, Chenjun Bai, Haozheng Li, Dafei Xie, Shi Chen, Yang Han, Jinhua Luo, Yang Li, Yumeng Ye, Jin Jia, Xin Huang, Hua Guan, Dingxin Long, Ruixue Huang, Shanshan Gao, Ping-Kun Zhou
Journal: Molecular Therapy (2023)
Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 and hepatitis B coinfection (ALLIANCE): a double-blind, multicentre, randomised controlled, phase 3 non-inferiority trial
Authors: Anchalee Avihingsanon, Hongzhou Lu, Chee Loon Leong, Chien-Ching Hung, Ellen Koenig, Sasisopin Kiertiburanakul, Man-Po Lee, Khuanchai Supparatpinyo, Fujie Zhang, Sophia Rahman, Michelle L D'Antoni, Hongyuan Wang, Jason T Hindman, Hal Martin, Jared M Baeten, Taisheng Li
Journal: The Lancet HIV (2023)
Update on the diagnosis of tuberculosis
Authors: Irina Kontsevaya, Andrea Maurizio Cabibbe, Daniela Maria Cirillo, Andrew R. DiNardo, Nicole Frahm, Stephen H. Gillespie, David Holtzman, Lennard Meiwes, Elisa Petruccioli, Maja Reimann, Morten Ruhwald, Wilber Sabiiti, Francesca Saluzzo, Elisa Tagliani, Delia Goletti
Journal: Clinical Microbiology and Infection (2023)
Suppressing <i>c-FOS</i> expression by G-quadruplex ligands inhibits osimertinib-resistant non-small cell lung cancers
Authors: Kai Lu, Hsin-Chiao Wang, Yi-Chen Tu, Cheng-Chung Chang, Pei-Jen Lou, Ta-Chau Chang, Jing-Jer Lin
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Osimertinib is the first-line therapy for patients with non-small cell lung cancer harboring epidermal growth factor receptor–activating alterations. Although osimertinib has been shown to elicit profound patient responses, cancer cells frequently develop additional alterations that sustain their proliferation capacity. This acquired resistance represents a substantial hurdle in precision medicine for patients with lung cancer. Methods The biological and cellular properties of the G-quadruplex ligand BMVC-8C3O and its anticancer activities were evaluated in non-small cell lung carcinomas. In addition, combined treatment with BMVC-8C3O and osimertinib was evaluated for its effects on the growth of osimertinib-resistant tumors in vivo. Results We demonstrate that BMVC-8C3O effectively suppresses c-FOS expression by stabilizing G-rich sequences located at the c-FOS promoter. The suppression c-FOS expression by BMVC-8C3O increases the sensitivity of acquired resistant cancer cells to osimertinib. Combining BMVC-8C3O and osimertinib has a synergistic effect in inhibiting the growth of acquired resistant cancers both in vitro and in mouse models. The combined inhibitory effect is not limited to BMVC-8C3O, either: several G-quadruplex ligands show varying levels of inhibition activity. We also show that simultaneous inhibition of both the c-FOS and PI3K/AKT pathways by BMVC-8C3O and osimertinib synergistically inhibits the growth of acquired resistant cancer cells. Conclusion These findings unveil a synthetic lethal strategy to prevent and inhibit epidermal growth factor receptor–altered lung cancers with acquired osimertinib resistance. G-quadruplex ligands have the potential to be integrated into current osimertinib-based treatment regimens.
Chitooligosaccharide reconstitutes intestinal mucus layer to improve oral absorption of water-soluble drugs
Authors: Yiming Qi, Ming Jin, Qing Li, Qinghua Wu, Zhiqian Liao, Menghao Wei, Xinyi Fan, Qianzhan Yang, Xiaohe Tian, Battaglia Giuseppe, Lei Luo
Journal: Journal of Controlled Release (2023)
Selective drug delivery to the retinal cells: Biological barriers and avenues
Authors: Eva Ramsay, Tatu Lajunen, Madhushree Bhattacharya, Mika Reinisalo, Kirsi Rilla, Heidi Kidron, Tetsuya Terasaki, Arto Urtti
Journal: Journal of Controlled Release (2023)

Retinal drug delivery is a challenging, but important task, because most retinal diseases are still without any proper therapy. Drug delivery to the retina is hampered by the anatomical and physiological barriers resulting in minimal bioavailability after topical ocular and systemic administrations. Intravitreal injections are current method-of-choice in retinal delivery, but these injections show short duration of action for small molecules and low target bioavailability for many protein, gene based drugs and nanomedicines. State-of-art delivery systems are based on prolonged retention, controlled drug release and physical features (e.g. size and charge). However, drug delivery to the retina is not cell-specific and these approaches do not facilitate intracellular delivery of modern biological drugs (e.g. intracellular proteins, RNA based medicines, gene editing). In this focused review we highlight biological factors and mechanisms that form the basis for the selective retinal drug delivery systems in the future. Therefore, we are presenting current knowledge related to retinal membrane transporters, receptors and targeting ligands in relation to nanomedicines, conjugates, extracellular vesicles, and melanin binding. These issues are discussed in the light of retinal structure and cell types as well as future prospects in the field. Unlike in some other fields of targeted drug delivery (e.g. cancer research), selective delivery technologies have been rarely studied, even though cell targeted delivery may be even more feasible after local administration into the eye.
Evaluation of common prescription analgesics and adjuvant analgesics as markers of suicide risk: a longitudinal population-based study in England
Authors: Danah Alothman, Edward Tyrrell, Sarah Lewis, Timothy Card, Andrew William Fogarty
Journal: The Lancet Regional Health - Europe (2023)

Analgesics prescriptions may provide a marker for identifying individuals at higher risk of suicide. In particular, awareness of which analgesics are implicated may help clinicians assess and modify risk.A case-control study in England using the Clinical Practice Research Datalink (for primary care records) linked with hospital and national mortality electronic registries. We included patients aged ≥15 who died by suicide between 2001 and 2019 (N = 14,515), to whom we individually matched 580,159 controls by suicide date and general practice (N = 594,674). Odds ratios (ORs) for suicide, controlled for age and sex, were assessed using conditional logistic regression.Suicide risks were highest in those prescribed adjuvant analgesics (pregabalin, gabapentin and carbamazepine) (adjusted OR 4.07; 95% confidence intervals CI: 3.62-4.57), followed by those prescribed opioids (adjusted OR 2.01; 95% CI: 1.88-2.15) and those prescribed non-opioid analgesics (adjusted OR 1.48; 95% CI: 1.39-1.58) compared to those not prescribed these medications. By individual analgesic, the highest suicide risks were seen in patients prescribed oxycodone (adjusted OR 6.70; 95% CI: 4.49-9.37); pregabalin (adjusted OR 6.50; 95% CI: 5.41-7.81); morphine (adjusted OR 4.54; 95% CI: 3.73-5.52); and gabapentin (adjusted OR 3.12; 95% CI: 2.59-3.75). Suicide risk increased linearly with the number of analgesic prescriptions in the final year (p < 0.01 based on the likelihood ratio test), and the more different analgesics categories were prescribed in the final year (p < 0.01 based on the likelihood ratio test).Analgesic prescribing was associated with higher suicide risk. This is a particular issue with regard to adjuvant non-opiate analgesics.There was no funding for this study.
Current and Future Perspectives on Computed Tomography Screening for Lung Cancer: A Roadmap From 2023 to 2027 From the International Association for the Study of Lung Cancer
Authors: Stephen Lam, Chunxue Bai, David R. Baldwin, Yan Chen, Casey Connolly, Harry de Koning, Marjolein A. Heuvelmans, Ping Hu, Ella A. Kazerooni, Harriet L. Lancaster, Georg Langs, Annette McWilliams, Raymond U. Osarogiagbon, Matthijs Oudkerk, Matthew Peters, Hilary A. Robbins, Liora Sahar, Robert A. Smith, Natthaya Triphuridet, John Field
Journal: Journal of Thoracic Oncology (2023)
AB1288 LONG-TERM AND BOOSTER VACCINATION RESPONSES IN PATIENTS WITH GIANT CELL ARTERITIS AND POLYMYALGIA RHEUMATICA
Authors: Y. Van Sleen, K. Van der Geest, A. Buisman, M. Sandovici, D. Van Baarle, E. Brouwer
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Vaccination remains essential in preventing morbidity of SARS-CoV-2 infections. We previously showed that &gt;10mg/day prednisolone and methotrexate use were associated with reduced antibody concentrations four weeks after primary vaccination in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) <sup>[1]</sup>. <h3>Objectives</h3> Here, we performed a follow-up study to measure the decay of antibody concentrations over time and the immunogenicity of SARS-CoV-2 booster vaccination. <h3>Methods</h3> GCA/PMR patients included in the primary vaccination (BNT162b2 or ChAdOx1) study were asked again to donate blood samples six months after primary vaccination (n=24) and one month after booster vaccination (n=46, BNT162b2 or mRNA1273). Data were compared to that of age-, sex-, and vaccine-matched controls (n=58 and n=42, respectively). <h3>Results</h3> Antibody concentrations decreased faster over time in GCA/PMR patients than in controls, but this decrease was not associated with treatment during primary vaccination. Post-booster antibody concentrations were comparable between patients and controls. Antibody concentrations post booster vaccination associated strongly with antibody concentrations post primary vaccination, but not with treatment during booster vaccination. However, the fold-change of post-booster vaccination showed a slight negative correlation with the post-primary vaccine antibodies. <h3>Conclusion</h3> These results indicate that patients with impaired vaccine responses after primary vaccination, have slightly stronger increases in humoral immunity after booster vaccination, but this is not enough to reach a similar protection. The decrease in humoral immunity, and subsequent increase after booster vaccination, is likely not impacted by prednisolone or methotrexate treatment. Rather, these treatments put the patients at an immunogenic disadvantage during primary SARS-CoV-2 vaccination, which is not fully repaired by a single booster vaccination. This longitudinal study in GCA/PMR patients stresses the importance of repeat booster vaccination for patients that used &gt;10mg/day prednisolone or methotrexate during primary vaccination. <h3>Reference</h3> [1]van Sleen Y, van der Geest, Kornelis SM, Reitsema RD, Esen I, Terpstra JH, Raveling-Eelsing E, et al. Humoral and cellular SARS-CoV-2 vaccine responses in patients with giant cell arteritis and polymyalgia rheumatica. RMD open 2022;8(2):e002479. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Yannick van Sleen: None declared, Kornelis van der Geest Speakers bureau: Speaker fees from Roche, Grant/research support from: Grant support from Abbvie, Annemarie Buisman: None declared, Maria Sandovici: None declared, Debbie van Baarle: None declared, Elisabeth Brouwer: None declared.
The entrancing role of dietary polyphenols against the most frequent aging‐associated diseases
Authors: Muhammad Ajmal Shah, Hafiza Ishmal Faheem, Ayesha Hamid, Rimsha Yousaf, Muhammad Haris, Uzma Saleem, Ghulam Mujtaba Shah, Reem H. Alhasani, Norah A. Althobaiti, Ifat Alsharif, Ana Sanches Silva
Journal: Medicinal Research Reviews (2023)

Aging, a fundamental physiological process influenced by innumerable biological and genetic pathways, is an important driving factor for several aging-associated disorders like diabetes mellitus, osteoporosis, cancer, and neurodegenerative diseases including Alzheimer's and Parkinson's diseases. In the modern era, the several mechanisms associated with aging have been deeply studied. Treatment and therapeutics for age-related diseases have also made considerable advances; however, for the effective and long-lasting treatment, nutritional therapy particularly including dietary polyphenols from the natural origin are endorsed. These dietary polyphenols (e.g., apigenin, baicalin, curcumin, epigallocatechin gallate, kaempferol, quercetin, resveratrol, and theaflavin), and many other phytochemicals target certain molecular, genetic mechanisms. The most common pathways of age-associated diseases are mitogen-activated protein kinase, reactive oxygen species production, nuclear factor kappa light chain enhancer of activated B cells signaling pathways, metal chelation, c-Jun N-terminal kinase, and inflammation. Polyphenols slow down the course of aging and help in combatting age-linked disorders. This exemplified in the form of clinical trials on specific dietary polyphenols in various aging-associated diseases. With this context in mind, this review reveals the new insights to slow down the aging process, and consequently reduce some classic diseases associated with age such as aforementioned, and targeting age-associated diseases by the activities of dietary polyphenols of natural origin.
Peer-based interventions to support transgender and gender diverse people’s health and healthcare access: A scoping review
Authors: Ashley Lacombe-Duncan, Luna Hughson, Emma Sophia Kay, Sydney Duncan, Camille Willbrandt
Journal: International Journal of Transgender Health (2023)

Pervasive health and healthcare disparities experienced by transgender (trans) and gender diverse (TGD) people require innovative solutions. Peer-based interventions may address disparities, and are an approach endorsed by TGD communities. However, the scope of the literature examining peer-based interventions to address health and healthcare access inclusive of TGD people is uncharted.
HIV and Cardiovascular Disease — An Ounce of Prevention
Authors: Matthew S. Freiberg
Journal: New England Journal of Medicine (2023)

Persons with human immunodeficiency virus (HIV) infection have up to two times the risk of cardiovascular disease as those without HIV infection.1 This risk is not explained by the presence of risk factors for atherosclerotic cardiovascular disease, nor is it eliminated by successful antiretroviral therapy and viral suppression.2 Assessing cardiovascular risk among persons with HIV infection has proved to be difficult because calculators for cardiovascular disease typically underestimate the risk in this population.3 This underestimation creates a challenge for health care providers. How can cardiovascular risk be reduced in a population that is assessed as being at low-to-moderate risk on . . .
Pitavastatin to Prevent Cardiovascular Disease in HIV Infection
Authors: Steven K. Grinspoon, Kathleen V. Fitch, Markella V. Zanni, Carl J. Fichtenbaum, Triin Umbleja, Judith A. Aberg, Edgar T. Overton, Carlos D. Malvestutto, Gerald S. Bloomfield, Judith S. Currier, Esteban Martinez, Jhoanna C. Roa, Marissa R. Diggs, Evelynne S. Fulda, Kayla Paradis, Stephen D. Wiviott, Borek Foldyna, Sara E. Looby, Patrice Desvigne-Nickens, Beverly Alston-Smith, Jorge Leon-Cruz, Sara McCallum, Udo Hoffmann, Michael T. Lu, Heather J. Ribaudo, Pamela S. Douglas
Journal: New England Journal of Medicine (2023)

The risk of cardiovascular disease is increased among persons with human immunodeficiency virus (HIV) infection, so data regarding primary prevention strategies in this population are needed.
Recent advances in the management of hepatocellular carcinoma
Authors: Kamya Sankar, Jun Gong, Arsen Osipov, Steven A. Miles, Kambiz Kosari, Nicholas N. Nissen, Andrew E. Hendifar, Ekaterina K. Koltsova, Ju Dong Yang
Journal: Clinical and Molecular Hepatology (2023)

Liver cancer remains a challenge of global health, being the 4th leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and is usually precipitated by chronic viral infections (hepatitis B and C), non-alcoholic steatohepatitis, heavy alcohol use, and other factors which may lead to chronic inflammation and cirrhosis of the liver. There have been significant advances in the systemic treatment options for HCC over the past decades, with several approvals of both immune checkpoint inhibitors and tyrosine kinase inhibitors in patients with preserved liver function. These advances have led to improvement in survival outcomes, with expected survival of greater than 18 months, in those with sensitive tumors, adequate liver function, and those functionally fit to receive sequential therapies. Several ongoing and promising trials are now evaluating combinational strategies with novel systemic agents and combinations of systemic therapy with locoregional therapy. In view of these trials, further advances in the treatment of HCC are foreseen in the near future.
Liquid biopsies for cancer: From bench to clinic
Authors: Zhenhui Chen, Chenghao Li, Yue Zhou, Yinghao Yao, Jiaqi Liu, Min Wu, Jianzhong Su
Journal: MedComm (2023)

Abstract Over the past two decades, liquid biopsy has been increasingly used as a supplement, or even, a replacement to the traditional biopsy in clinical oncological practice, due to its noninvasive and early detectable properties. The detections can be based on a variety of features extracted from tumor‑derived entities, such as quantitative alterations, genetic changes, and epigenetic aberrations, and so on. So far, the clinical applications of cancer liquid biopsy mainly aimed at two aspects, prediction (early diagnosis, prognosis and recurrent evaluation, therapeutic response monitoring, etc.) and intervention. In spite of the rapid development and great contributions achieved, cancer liquid biopsy is still a field under investigation and deserves more clinical practice. To better open up future work, here we systematically reviewed and compared the latest progress of the most widely recognized circulating components, including circulating tumor cells, cell‐free circulating DNA, noncoding RNA, and nucleosomes, from their discovery histories to clinical values. According to the features applied, we particularly divided the contents into two parts, beyond epigenetics and epigenetic‐based. The latter was considered as the highlight along with a brief overview of the advances in both experimental and bioinformatic approaches, due to its unique advantages and relatively lack of documentation.
The Application of 18F-FES PET in Clinical Cancer Care
Authors: Ya-Ting Huang, Tom Wei-Wu Chen, Li-Yu Chen, Ya-Yao Huang, Yen-Shen Lu
Journal: Clinical Nuclear Medicine (2023)

Introduction [ 18 F]fluoroestradiol (FES) can be used for the noninvasive visualization and quantification of tumor estrogen receptor (ER) expression and activity and was FDA-approved as a diagnostic agent in May 2022 for detecting ER-positive lesions in patients with recurrent or metastatic breast cancer. PET imaging was also used to detect ER-positive lesions and malignancy among patients with uterine, ovarian, and other ER-positive solid tumors. We conducted a systemic review of the studies on FES PET imaging used among patients with cancer not limited to breast cancer to better understand the application of FES PET imaging. Methods PubMed/MEDLINE and Cochrane Library databases were used to perform a comprehensive and systematic search and were updated until August 15, 2022. Two authors independently reviewed the titles and abstracts of the retrieved articles by using the search algorithm and selected the articles based on the inclusion and exclusion criteria. All statistical analyses were conducted using R statistical software. Results Forty-three studies with 2352 patients were included in the qualitative synthesis, and 23 studies with 1388 patients were included in the quantitative analysis, which estimated the FES-positive detection rate. Thirty-two studies (77%) included breast cancer patients in 43 included studies. The FES SUV mean was higher in patients with endometrial cancer (3.4–5.3) than in those with breast cancer (2.05) and uterine sarcoma (1.1–2.6). The pooled detection rates of FES PET imaging were 0.80 for breast and 0.84 for ovarian cancer patients, both similar to that of 18 F-FDG. The FES uptake threshold of 1.1 to 1.82 could detect 11.1% to 45% ER heterogeneity, but the threshold of FES uptake did not have consistent predictive ability for prognosis among patients with breast cancer, unlike uterine cancer. However, FES uptake can effectively predict and monitor treatment response, especially endocrine therapy such as estradiol, ER-blocking agents (fulvestrant and tamifoxen), and aromatase inhibitors (such as letrozole and Z-endoxifen). Conclusions [ 18 F]fluoroestradiol PET is not only a convenient and accurate diagnostic imaging tool for detecting ER-expressing lesions in patients with breast and ovarian cancer but also among patients with uterine cancer. [ 18 F]fluoroestradiol PET is a noninvasive predictive and monitoring tool for treatment response and prognosis.